Abstract

Background: CD44, a cell surface proteoglycan receptor, plays an important role in modulating oral squamous cell carcinoma (OSCC) cell functions. The recent identification of CD44 as a cancer stem cell marker led us to hypothesize that cleavage of CD44 may alter OSCC cell-matrix interactions and anoikis resistance, and thereby promote a metastatic phenotype in OSCC.

Methods: Anoikis-resistant cells were developed by maintaining human OSCC (UM-SCC 14A) cells under suspension culture conditions in polyhydroxyethylmethacrylate (poly-HEMA) coated plates. Anoikis sensitive control cells were maintained in adherent culture conditions. CD44 cleavage was blocked by the use of matrix metalloproteinase (MMP) chemical inhibitors, including ADAM-17 and ADAM-10. Western blot analysis was used to examine the relative levels of CD44 among the adherent and anoikis-resistant cells.

Results: This study showed that anoikis resistant OSCC cells exhibit higher levels of CD44 cleavage than their adherent counterparts. The study also showed that ADAM-10 and ADAM-17 chemical inhibitors blocked CD44 cleavage and the formation of anoikis-resistant multicellular aggregates in OSCC cells.

Conclusions: CD44 cleavage plays a crucial role in promoting the anoikis resistant phenotype in OSCC cells, suggesting that CD44 may significantly contribute to OSCC tumor initiation and metastasis. (Supported by NIH RO1 DE014429 to YLK)